title: Regulation of autophagy and apoptosis in response to angiotensin II in HL-1 cardiomyocytes.
abstract: BACKGROUND
  Autophagy and apoptosis are two important regulators of cell survival, and are often observed simultaneously in response to noxious stimuli. Anoxia is a known stimulus for autophagy and apoptosis, and angiotensin (Ang) II is a major mediator of anoxic injury. However, specific responses to anoxia and Ang II in terms of occurrence of autophagy and apoptosis have still not been delineated.
  
  
  RESULTS
  We observed that autophagy (measured as LC3 staining, and Beclin-1 and p62 Western blotting) was an early response and apoptosis (measured as TUNEL staining, and Annexin V and Smac/Diablo Western blotting) became dominant as the duration of anoxia was prolonged. Autophagy also occurred quickly in response to low concentrations of Ang II. When exposed to high concentrations of Ang II, a significant number of cells developed apoptosis, while autophagy response decreased. Ang II-mediated apoptosis was blocked by Ang II type 1 receptor (AT1R) blocker losartan as well as by the AT2R blocker PD123319. Ang II-induced autophagy was blocked by losartan, but not by PD123319.
  
  
  CONCLUSIONS
  Exposure to Ang II, a mediator of anoxic injury, initiates a rapid autophagy response, perhaps in an attempt to protect tissues from the impending noxious effects. However, when anoxia (and thereby release of Ang II) is prolonged, the process of apoptosis dominates. These processes will determine the outcome of cardiomyocyte well-being in states of hypoxia.
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, Henan, China; Division of Cardiology, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address: Xwang2@uams.edu.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Dai
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Federico
authors.initials: F
authors.lastname: Mercanti
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D015687:Cell Hypoxia; D002460:Cell Line; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D006360:Heat-Shock Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D000804:Angiotensin II
keywords: Angiotensin II; Anoxia; Apoptosis; Autophagy; HL-1 cardiomyocytes